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Titanium dioxide nanoparticles impair the inner blood-retinal barrier and retinal electrophysiology through rapid ADAM17 activation and claudin-5 degradation
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Abstract
Background:Depending on their distinct properties, titanium dioxide nanoparticles (TiO2-NPs) are manufacturedextensively and widely present in our daily necessities, with growing environmental release and public concerns. Insunscreen formulations, supplementation of TiO2-NPs may reach up to 25% (w/w). Ocular contact with TiO2-NPsmay occur accidentally in certain cases, allowing undesirable risks to human vision. This study aimed to understandthe barrier integrity of retinal endothelial cells in response to TiO2-NP exposure. bEnd.3 cells and human retinalendothelial cells (HRECs) were exposed to TiO2-NP, followed by examination of their tight junction componentsand functions.Results: TiO2-NP treatment apparently induced a broken structure of the junctional plaques, conferring decreasedtransendothelial electrical resistance, a permeable paracellular cleft, and improved cell migration in vitro. This mightinvolve rapid activation of metalloproteinase, a disintegrin and metalloproteinase 17 (ADAM17), and ADAM17-mediated claudin-5 degradation. For the in vivo study, C57BL/6 mice were administered a single dose of TiO2-NPintravitreally and then subjected to a complete ophthalmology examination. Fluorescein leakage and reducedblood flow at the optical disc indicated a damaged inner blood-retinal barrier induced by TiO2-NPs. Inappreciablechange in the thickness of retinal sublayers and alleviated electroretinography amplitude were observed in theTiO2-NP-treated eyes.Conclusions: Overall, our data demonstrate that TiO2-NP can damage endothelial cell function, thereby affectingretinal electrophysiology.
Item Type: | Article |
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Authors/Creators: | Chan, YJ and Liao, PL and Tsai, CH and Cheng, YW and Lin, FL and Ho, JD and Chen, CY and Li, CH |
Keywords: | titanium dioxide nanoparticles, endothelial cells, claudin-5, ADAM17, blood-retinal barrier |
Journal or Publication Title: | Particle and Fibre Toxicology |
Publisher: | BioMed Central Ltd. |
ISSN: | 1743-8977 |
DOI / ID Number: | 10.1186/s12989-020-00395-7 |
Copyright Information: | Copyright 2021 the Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/ |
Item Statistics: | View statistics for this item |
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